The overall goal of the proposed research is to develop and utilize new methodology to synthesize biologically active mono-, bis-, and polycyclams and oxocyclams (14 membered tetraazamacrocycles) and their metal complexes and, with appropriate collaboration, assess their ability to selectively bind and cleave nucleic acids, to catalyze phosphate diester hydrolysis, to produce complexes suitable for use as biological imaging agents, and finally to synthesize complexes having antibacterial and anti-viral activity. It is emphasized that the major thrust of this proposal is synthetic. Specific aims include (1) the synthesis of monocyclams and their metal complexes having intercalating groups at the 6 and 13 positions, with defined sterochemistry, for use as bis-intercalators for selective binding and selective oxidative cleavage of nuclei acids, as well as the assessment of their antibiotic and antitumor activity; (2) the synthesis of bis-cyclams lined at the 6 and 13 positions by various bridging groups, having defined interring distances and dihedral angles, as well as their homo- and heterobimetallic complexes, for use as bimetallic catalysts of phosphate diester hydrolysis, biological imaging agents, and anti-viral agents; (3) the synthesis of bis cyclams bridge by hydrophilic groups to increase water solubility and bioavailability, by polyether linkages to provide systems which can complex both transition and alkali metals; and (4) the synthesis of peripherally functionalized bis-cyclams. Rapid, efficient, high yield synthesis of these new classes of macrocyclic compound and complexes will be the primary focus of the proposed research.